• Title/Summary/Keyword: Preclinical studies

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Initial Dosimetry of a Prototype Ultra-High Dose Rate Electron-Beam Irradiator for FLASH RT Preclinical Studies

  • Hyun Kim;Heuijin Lim;Sang Koo Kang;Sang Jin Lee;Tae Woo Kang;Seung Wook Kim;Wung-Hoa Park;Manwoo Lee;Kyoung Won Jang;Dong Hyeok Jeong
    • Progress in Medical Physics
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    • v.34 no.3
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    • pp.33-39
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    • 2023
  • Purpose: FLASH radiotherapy (RT) using ultra-high dose rate (>40 Gy/s) radiation is being studied worldwide. However, experimental studies such as preclinical studies using small animals are difficult to perform due to the limited availability of irradiation devices and methods for generating a FLASH beam. In this paper, we report the initial dosimetry results of a prototype electron linear accelerator (LINAC)-based irradiation system to perform ultra-high dose rate (UHDR) preclinical experiments. Methods: The present study used the prototype electron LINAC developed by the Research Center of Dongnam Institute of Radiological and Medical Sciences (DIRAMS) in Korea. We investigated the beam current dependence of the depth dose to determine the optimal beam current for preclinical experiments. The dose rate in the UHDR region was measured by film dosimetry. Results: Depth dose measurements showed that the optimal beam current for preclinical experiments was approximately 33 mA, corresponding to a mean energy of 4.4 MeV. Additionally, the average dose rates of 80.4 Gy/s and 162.0 Gy/s at a source-to-phantom surface distance of 30 cm were obtained at pulse repetition frequencies of 100 Hz and 200 Hz, respectively. The dose per pulse and instantaneous dose rate were estimated to be approximately 0.80 Gy and 3.8×105 Gy/s, respectively. Conclusions: Film dosimetry verified the appropriate dose rates to perform FLASH RT preclinical studies using the developed electron-beam irradiator. However, further research on the development of innovative beam monitoring systems and stabilization of the accelerator beam is required.

Classical, Non-Clinical, and Clinical Evidence of Yokukansan for Alleviating Aggression: Scoping Review (치매 환자의 공격성 관리에 활용가능한 억간산(抑肝散)의 고전적, 비임상적, 임상적 근거현황)

  • Lee, Dong-Yoon;Kim, Je-Beom;Ha, Da-Jung;Kwon, Chan-Young
    • Journal of Oriental Neuropsychiatry
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    • v.32 no.2
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    • pp.111-127
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    • 2021
  • Objectives: To review and analyze clinical and preclinical evidence of effectiveness, safety, and underlying mechanisms of yokukansan (YKS), a herbal medicine, in alleviating aggression. Methods: Classical records on YKS were searched in the Korean Traditional Medicine Knowledge Database (KTMKD). By searching five electronic databases, prospective clinical studies and preclinical studies of YKS for alleviating aggression/agitation published up to March 30, 2021 were included. Results: Only two classical records on YKS were found from the KTMKD. A total of 11 clinical studies and 15 preclinical studies were found from the five electronic databases. Among 11 clinical studies, seven enrolled patients with dementia and four enrolled patients with other neuropsychiatric disorders. Most clinical studies reported significant improvement in one or more outcomes related to aggression in the YKS group after treatment. Among 15 preclinical studies, all studies except two reported a significant decrease in aggression/agitation-related behavior of YKS or yokukansankachimpihange. Suggested underlying mechanisms of YKS or yokukansankachimpihange for aggression/agitation in these studies included regulation of serotonin receptor, amelioration of abnormal glucocorticoid level related to the hypothalamic-pituitary-adrenal axis, regulation of orexin secretion, amelioration of degeneration in brain cells including glia cells, and suppression of excessive glutamatergic or dopaminergic activity. Conclusions: There were some clinical and preclinical evidence supporting the effectiveness and safety of YKS for alleviating aggression. Given that aggression is the most frequent and destructive symptoms of behavioral and psychological symptoms of dementia, applicability of YKS as a herbal medicine should be further investigated in future high-quality research.

P-Glycoprotein-Based Drug-Drug Interactions: Preclinical Methods and Relevance to Clinical Observations

  • Aszalos, Adorjan
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.127-135
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    • 2004
  • Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.

The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis

  • Kim, Yunna;Cho, Seung-Hun
    • Journal of Ginseng Research
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    • v.45 no.3
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    • pp.420-432
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    • 2021
  • Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

The Effects of Preclinical Clinical Performance Examination on Nursing Students' Confidence in Nursing Skills and Critical Thinking Competence (임상실습 전 임상수행능력평가(CPX)가 간호대학생의 핵심기본간호술 자신감과 비판적 사고능력에 미치는 효과)

  • Park, Jeong Sook;Choi, Mi Jung;Jang, Soon Yang
    • The Journal of Korean Academic Society of Nursing Education
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    • v.21 no.1
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    • pp.75-85
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    • 2015
  • Purpose: The purpose of this study was to investigate the effects of preclinical clinical performance examination (CPX) on nursing students' confidence in their nursing skills and critical thinking competence. Methods: The design of this research was one-group pretest-posttest, and the participants were 112 nursing students. The preclinical CPX consisted of a clinical examination, patient-nurse relationship, oral test of related knowledge, written test of the nursing process, and debriefing using comprehensive scenarios based on real patient cases. The confidence of nursing skills consisted of an 8-item NRS and the critical thinking competence consisted of a 12-item 4-point scale developed by researchers and measured in both the pretest and posttest. The collected data were analyzed using paired t-tests, ANOVA, and Pearson correlation coefficients. Results: The score for confidence in nursing skills (t=10.60, p<.001) and that for critical thinking competence (t=7.03, p<.001) increased significantly after preclinical CPX. Conclusion: This study showed that preclinical CPX was effective in improving nursing students' confidence in their nursing skills and critical thinking competence. Therefore, preclinical CPX is expected to be utilized in nursing practice education. Additional studies including those on control groups are recommended to compare differences between the preclinical CPX group and control group.

Electron beam scattering device for FLASH preclinical studies with 6-MeV LINAC

  • Jeong, Dong Hyeok;Lee, Manwoo;Lim, Heuijin;Kang, Sang Koo;Lee, Sang Jin;Kim, Hee Chang;Lee, Kyohyun;Kim, Seung Heon;Lee, Dong Eun;Jang, Kyoung Won
    • Nuclear Engineering and Technology
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    • v.53 no.4
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    • pp.1289-1296
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    • 2021
  • In this study, an electron-scattering device was fabricated to practically use the ultra-high dose rate electron beams for the FLASH preclinical research in Dongnam Institute of Radiological and Medical Sciences. The Dongnam Institute of Radiological and Medical Sciences has been involved in the investigation of linear accelerators for preclinical research and has recently implemented FLASH electron beams. To determine the geometry of the scattering device for the FLASH preclinical research with a 6-MeV linear accelerator, the Monte Carlo N-particle transport code was exploited. By employing the fabricated scattering device, the off-axis and depth dose distributions were measured with radiochromic films. The generated mean energy of electron beams via the scattering device was 4.3 MeV, and the symmetry and flatness of the off-axis dose distribution were 0.11% and 2.33%, respectively. Finally, the doses per pulse were obtained as a function of the source to surface distance (SSD); the measured dose per pulse varied from 4.0 to 0.2 Gy/pulse at an SSD range of 20-90 cm. At an SSD of 30 cm with a 100-Hz repetition rate, the dose rate was 180 Gy/s, which is sufficient for the preclinical FLASH studies.

Hippocampus and Schizophrenia (해마와 정신분열병)

  • Chung, Young Chul
    • Korean Journal of Biological Psychiatry
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    • v.10 no.1
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    • pp.20-44
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    • 2003
  • Schizophrenics suffer not only psychotic symptoms but also cognitive deficits such as an attentional difficulty, memory impairment, poor abstraction, etc. These cognitive abnormalities have been reported to be significantly related to the social and occupational outcome in schizophrenia. Thus, it is important to explore the cause and pathophysiology for the cognitive abnormalities in patients with schizophrenia. In this regard, hippocampus is one of the most promising brain areas to search for the clue because it is closely involved in memory related function. In fact, during the past several decades, there have been extensive studies supporting hippocampal abnormalities as a cause of schizophrenia in both clinical and preclinical field. In this review, basic anatomical knowledge about hippocampus and major findings of preclinical and clinical studies which investigated the correlation between schizophrenia and hippocampus were highlighted. The contents are 1) anatomical structure of hippocampus, 2) neuronal pathway and receptor distribution in hippocampus, 3) function of hippocampus, 4) hippocampal animal model for schizophrenia, 5) hippocampus-related studies on antipsychotic drugs, and 6) clinical studies in hippocampus in patients with schizophrenia.

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Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells

  • Kim, Ji Sung;Kim, Yong Guk;Pyo, Minji;Lee, Hong Kyung;Hong, Jin Tae;Kim, Youngsoo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.58-65
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    • 2015
  • Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.